Sulfonatocalixarene Promotes Drug Assembly Based on Supramolecular Host•–Guest Complexation in Aqueous Solution

Supramolecular nano-sized assemblies with high structural stability are designed based on hostguest complexation in aqueous solution using sulfonatocalix[n]arenes (SXCn) as macrocyclic hosts and three drug molecules (doxepin, desipramine, and promazine). The supramolecular complexation between SCX4 and the drug molecules is established by means of fluorescence displacement titration and isothermal titration calorimetry. The complexation is primarily driven by ion-ion interactions between the negatively charged rim of SCX4 and the ammonium group of the guest molecule as well as C─H─π interactions. Despite the high-water solubility of SCX4 and the drug molecules, their combination reveals the formation of supramolecular assembly at low millimolar concentrations. These assemblies exhibit a thermoresponsive behavior, highlighting their potential for the design of functional materials.